3.1. Study Population
is a diagram of the selection steps for allocating patients to control or intervention and application of inclusion and exclusion criteria. During the three month trial period, 1,488 of 11,128 admitted adults experienced a triggering change of serum creatinine over 48 hours. We enrolled 540 cases; 278 were randomized to the control group, and 262 were randomized to the intervention group. The blinded outcomes assessment pharmacist identified 82 control and 62 intervention cases that met additional exclusion criteria that could not be determined electronically at the time of randomization; we included 396 cases in the final outcomes assessment. We compared demographic characteristics, including age, sex, race, admitting service, and admission to an intensive care unit, and comorbidities, which the initial outcomes assessment study pharmacist classified, between the control and intervention groups to ensure that the study groups were similar (). We found no statistical difference between groups for any variable evaluated.
Study population demographics for analyzed acute kidney injury surveillance cases
3.2. Evaluation of Adverse Drug Events
We evaluated 196 control cases with 1303 medication orders and 200 intervention cases with 1396 medication orders. Agreement between the two outcomes adjudication physicians was 93.97% for pADEs (kappa=0.88) and 96.55% for ADEs (kappa=0.93). depicts the detailed breakdown of pADEs and ADEs after adjudication and consensus. The adjudication committee determined 76 (38.8%) control and 67 (33.5%) intervention cases experienced a pADE or ADE (RR=0.86 [0.66, 1.12], p=0.3) and 104 (7.98%) control and 99 (7.09%) intervention medication orders had an associated pADE or ADE (RR=0.88 [0.68, 1.16], p=0.4). Among cases who experienced at least one pADE or ADE in the control group, 55 (72.4%) experienced one, 15 (19.7%) experienced two, 5 (6.6%) experienced three, and 1 (1.32%) experienced four events; in the intervention group, 41 (61.2%) experienced one, 20 (29.9%) experienced two, and 6 (9.0%) experienced three events.
Evaluation of potential adverse drug events and adverse drug events
The total events included 52 (26.5%) control and 46 (23.0%) intervention cases experiencing a pADE (RR=0.87 [0.61, 1.22], p=0.4), and 68 (5.22%) control and 63 (4.51%) intervention medication orders having an associated pADE (RR=0.86 [0.62, 1.21], p=0.4). Frequent responses for pADEs categorized as “other” included “dose and interval change inappropriate for trough level” and “interacted with another prescribed medication”.
Lab-only ADEs occurred for 13 (6.6%) control and 16 (8.0%) intervention cases (RR=1.21 [0.60, 2.44], p=0.6); 14 (1.07%) control and 16 (1.15%) intervention medication orders had an associated lab-only ADE (RR=1.07 [0.52, 2.18], p=0.9). Actual ADEs occurred for 22 (11.2%) control and 19 (9.5%) intervention cases (RR=0.85 [0.47, 1.51], p=0.6); 22 (1.69%) control and 20 (1.43%) intervention medication orders had an associated actual ADE (RR=0.85 [0.47, 1.55], p=0.6). Severity and preventability of pADEs and ADEs was not significant between control and intervention groups ().
Evaluation of potential adverse drug events and adverse drug events
Among drugs or drug groups with at least ten orders in the control and intervention groups, errors most commonly occurred for vancomycin, beta lactam antibiotics, angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), quinolones, and angiotensin II receptor blockers (ARBs) comprising 22.2%, 15.3%, 12.3%, 9.4%, 8.9%, and 5.4% of orders resulting in a pADE or ADE respectively.
3.3. Evaluation of Provider Responses
For medications active at the time of patient’s triggering serum creatinine change or ordered after the event, we compared the time to provider response, defined as drug modification or discontinuation, using the log-rank test. While the time to response was shorter in the intervention group compared to the control group for medications, overall response times were highly variable, and we did not find any statistically significant differences between the control and intervention groups. shows the resulting median times to response, hazard ratios, and p-values. Kaplan-Meier curves for these results are shown in .
Evaluation of surveillance and provider response
3.4. Study Pharmacist Interactions with the Surveillance Tool
During the 3-month study period, 273 intervention patients appeared on the surveillance tool. The study pharmacist viewed the surveillance tool on 67 days (56 weekdays). Of the displayed intervention patients, 234 (85.7%) were reviewed by the study pharmacist, with an average of 10.75 patients reviewed each day the surveillance tool was monitored. Monitoring occurred between 08:00 and 16:00, although the study pharmacist primarily checked the surveillance tool in the afternoon, after providing teams had completed rounds, updated medication orders, and entered EMR notes, and laboratory results had returned. During a week of direct observation, the pharmacist spent 71 minutes monitoring the surveillance tool on Monday, and a mean of 16.75 minutes on the remaining days (25 on Tuesday, 9 on Wednesday, 15 on Thursday, and 18 on Friday).
The study pharmacist recommended an intervention for 43 (18.4%) cases, including 70 medication-specific recommendations and 8 patient-specific recommendations. Most cases without an intervention did not require a dose change; frequencies of recommended patient and medication interventions are described in . Medication recommendations categorized as “other” (9 medications) included correcting the patient’s weight, holding the medication, and monitoring for sedation. Patient recommendations categorized as “other” (2 cases) included redrawing serum creatinine, monitoring for sedation and treatment failure, discontinuing oral potassium, and adding height and weight.
Study pharmacist recommendations
The study pharmacist most frequently indicated use of text pages and verbal communication to contact the providing team; recorded contact included 26 text pages, 28 verbal communications, and 1 EMR note. EMR notes were used when the providing team was unavailable (e.g. providing team does not have an attending on campus, or provider did not respond to text page). Providers agreed to make the recommended changes for 24 interventions (77% of recorded responses), the study pharmacist made changes to the orders directly in the CPOE system for 5 interventions (16%), and the provider disagreed with recommendation for 2 interventions (6%). The study pharmacist submitted 157 surveillance tool comments for 102 cases. The comments frequently summarized patient comorbidities, laboratory values and trends, and indications; served as reminders for continued monitoring; and elaborated recommendations.